Q6Y4S4 (KISS1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Metastasis-suppressor KiSS-1

Alternative name(s):
Kisspeptin-1

Cleaved into the following 2 chains:

1. Metastin
   Alternative name(s):
   Kisspeptin-52
2. Kisspeptin-10
   Alternative name(s):
   Metastin45-54

Gene names

Name:

Kiss1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	130 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Metastasis suppressor protein. May regulate events downstream of cell-matrix adhesion, perhaps involving cytoskeletal reorganization. Generates a C-terminally amidated peptide, metastin which functions as the endogenous ligand of the G-protein coupled receptor GPR54. Activation of the receptor inhibits cell proliferation and cell migration, key characteristics of tumor metastasis. The receptor is also essential for normal gonadotropin-released hormone physiology and for puberty. The hypothalamic KiSS1/GPR54 system is a pivotal factor in central regulation of the gonadotropic axis at puberty and in adulthood. Intracerebroventricular administration induces an increase in serum LH and FSH levels in prepubertal male and female as well as in adult animals. Ref.6 Ref.8 Ref.9 Ref.11
Subcellular location	Secreted.
Tissue specificity	Weak in all tissue types with highest levels in lung and 15- 17-day embryos. Expressed in areas of the hypothalamus implicated in the neuroendocrine regulation of gonadotropin secretion, including the anteroventral periventricular nucleus, the periventricular nucleus, and the arcuate nucleus. Ref.1 Ref.6
Disruption phenotype	Animals are viable and healthy with no apparent abnormalities but fail to undergo sexual maturation. Mutant female do not progress through the estrous cycle, have thread-like uteri and small ovaries, and do not produce mature Graffian follicles. Mutant males have small testes, and spermatogenesis arrested mainly at the early haploid spermatid stage. Both sexes have low circulating gonadotropin (LH and FSH) and sex steroid (beta-estradiol or testosterone) hormone levels. Migration of GnRH neurons into the hypothalamus appears normal with appropriate axonal connections to the median eminence and total GnRH content. The hypothalamic-pituitary axis is functional, as shown by robust LH secretion after peripheral administration of kisspeptin. Ref.12
Sequence similarities	Belongs to the KISS1 family.
Sequence caution	The sequence AAO64981.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Alternative splicing
Domain	Signal
PTM	Amidation Cleavage on pair of basic residues Disulfide bond Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	elevation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway Inferred from electronic annotation. Source: Compara generation of ovulation cycle rhythm Inferred from electronic annotation. Source: Compara negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of MAPK cascade Inferred from electronic annotation. Source: Compara positive regulation of growth hormone secretion Inferred from electronic annotation. Source: Compara positive regulation of luteinizing hormone secretion Inferred from electronic annotation. Source: Compara positive regulation of synaptic transmission Inferred from electronic annotation. Source: Compara
Cellular_component	apical plasma membrane Inferred from electronic annotation. Source: Compara cytoplasm Inferred from electronic annotation. Source: Compara extracellular space Inferred from electronic annotation. Source: Compara neuron projection Inferred from electronic annotation. Source: Compara neuronal cell body Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q6Y4S4-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q6Y4S4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     25-28: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	Potential
	Chain	20 – 130	111	Metastasis-suppressor KiSS-1		PRO_0000021552
	Peptide	68 – 119	52	Metastin		PRO_0000021553
	Peptide	110 – 119	10	Kisspeptin-10		PRO_0000021554
Regions
	Region	110 – 119	10	Essential for receptor binding and receptor activation
Amino acid modifications
	Modified residue	110	1	Phosphotyrosine By similarity
	Modified residue	119	1	Tyrosine amide By similarity
	Disulfide bond	71 ↔ 85		Potential
Natural variations
	Alternative sequence	25 – 28	4	Missing in isoform 2.		VSP_012957

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2005. Version 2. Checksum: AC9D30CF84B4F41B	FASTA	130	14,117
	10 20 30 40 50 60 MISMASWQLL LLLCVATYGE PLAKVAPLVK PGSTGQQSGP QELVNAWEKE SRYAESKPGS 70 80 90 100 110 120 AGLRARRSSP CPPVEGPAGR QRPLCASRSR LIPAPRGAVL VQREKDLSTY NWNSFGLRYG 130 RRQAARAARG
	Isoform 2 [UniParc]. Checksum: A71956212746F37A	FASTA	126	13,737
	10 20 30 40 50 60 MISMASWQLL LLLCVATYGE PLAKVKPGST GQQSGPQELV NAWEKESRYA ESKPGSAGLR 70 80 90 100 110 120 ARRSSPCPPV EGPAGRQRPL CASRSRLIPA PRGAVLVQRE KDLSTYNWNS FGLRYGRRQA ARAARG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and characterization of mouse metastasis-suppressor KiSS1 and its G-protein-coupled receptor." Stafford L.J., Xia C., Ma W., Cai Y., Liu M. Cancer Res. 62:5399-5404(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, TISSUE SPECIFICITY. Strain: 129S6/SvEvTac. Tissue: Brain.
[2]	"Expression of KiSS-1, a metastasis suppressor gene, in trophoblast giant cells of the rat placenta." Terao Y., Kumano S., Takatsu Y., Hattori M., Nishimura A., Ohtaki T., Shintani Y. Biochim. Biophys. Acta 1678:102-110(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: Embryo.
[3]	"Identification and characterization of metastin in the mouse spinal cord." Ohsawa M., Chi M., Ohtsubo Y., Brailoiu G.C., Yang J., Chang J., Dun N.J. Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Strain: ICR. Tissue: Brain.
[4]	"The genesis of the human KISS1." Xie H., Bonaldo M.F., Soares M.B. Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Strain: C57BL/6J. Tissue: Placenta.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[6]	"A role for kisspeptins in the regulation of gonadotropin secretion in the mouse." Gottsch M.L., Cunningham M.J., Smith J.T., Popa S.M., Acohido B.V., Crowley W.F., Seminara S., Clifton D.K., Steiner R.A. Endocrinology 145:4073-4077(2004) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, ROLE IN THE REGULATION OF GONADOTROPIN SECRETION.
[7]	"Kisspeptin activation of gonadotropin releasing hormone neurons and regulation of KiSS-1 mRNA in the male rat." Irwig M.S., Fraley G.S., Smith J.T., Acohido B.V., Popa S.M., Cunningham M.J., Gottsch M.L., Clifton D.K., Steiner R.A. Neuroendocrinology 80:264-272(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN REGULATION OF GONADOTROPIN SECRETION.
[8]	"Advanced vaginal opening and precocious activation of the reproductive axis by KiSS-1 peptide, the endogenous ligand of GPR54." Navarro V.M., Fernandez-Fernandez R., Castellano J.M., Roa J., Mayen A., Barreiro M.L., Gaytan F., Aguilar E., Pinilla L., Dieguez C., Tena-Sempere M. J. Physiol. (Lond.) 561:379-386(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"Characterization of the potent luteinizing hormone-releasing activity of KiSS-1 peptide, the natural ligand of GPR54." Navarro V.M., Castellano J.M., Fernandez-Fernandez R., Tovar S., Roa J., Mayen A., Nogueiras R., Vazquez M.J., Barreiro M.L., Magni P., Aguilar E., Dieguez C., Pinilla L., Tena-Sempere M. Endocrinology 146:156-163(2005) [PubMed] [Europe PMC] [Abstract] Cited for: ROLE IN LUTEINIZING HORMONE SECRETION.
[10]	"Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54." Messager S., Chatzidaki E.E., Ma D., Hendrick A.G., Zahn D., Dixon J., Thresher R.R., Malinge I., Lomet D., Carlton M.B., Colledge W.H., Caraty A., Aparicio S.A.J.R. Proc. Natl. Acad. Sci. U.S.A. 102:1761-1766(2005) [PubMed] [Europe PMC] [Abstract] Cited for: DIRECT STIMULATION OF GONADOTROPIN-RELEASING HORMONE RELEASE.
[11]	"Effects of KiSS-1 peptide, the natural ligand of GPR54, on follicle-stimulating hormone secretion in the rat." Navarro V.M., Castellano J.M., Fernandez-Fernandez R., Tovar S., Roa J., Mayen A., Barreiro M.L., Casanueva F.F., Aguilar E., Dieguez C., Pinilla L., Tena-Sempere M. Endocrinology 146:1689-1697(2005) [PubMed] [Europe PMC] [Abstract] Cited for: ROLE IN FOLLICLE-STIMULATING HORMONE SECRETION.
[12]	"Hypogonadotropic hypogonadism in mice lacking a functional Kiss1 gene." d'Anglemont de Tassigny X., Fagg L.A., Dixon J.P., Day K., Leitch H.G., Hendrick A.G., Zahn D., Franceschini I., Caraty A., Carlton M.B., Aparicio S.A., Colledge W.H. Proc. Natl. Acad. Sci. U.S.A. 104:10714-10719(2007) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF472576 mRNA. Translation: AAP13356.1. AY182231 mRNA. Translation: AAO64981.1. Different initiation. AB162440 mRNA. Translation: BAD36756.1. AY707858 mRNA. Translation: AAW34131.1. BC117046 mRNA. Translation: AAI17047.1. BC119348 mRNA. Translation: AAI19349.1.
IPI	IPI00265221. IPI00553415.
RefSeq	NP_839991.2. NM_178260.3.
UniGene	Mm.458301.
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	Q6Y4S4.
Proteomic databases
PRIDE	Q6Y4S4.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000007433; ENSMUSP00000007433; ENSMUSG00000091251. ENSMUST00000178033; ENSMUSP00000136746; ENSMUSG00000091251.
GeneID	280287.
KEGG	mmu:280287.
UCSC	uc007cqd.1. mouse.
Organism-specific databases
CTD	3814.
MGI	MGI:2663985. Kiss1.
Phylogenomic databases
GeneTree	ENSGT00390000008827.
HOVERGEN	HBG052261.
OMA	SRQIPAP.
Gene expression databases
ArrayExpress	Q6Y4S4.
Bgee	Q6Y4S4.
Genevestigator	Q6Y4S4.
GermOnline	ENSMUSG00000041717. Mus musculus.
Family and domain databases
InterPro	IPR020207. Metastasis-suppressor_KiSS-1. [Graphical view]
ProDom	PD088121. Metastasis-suppressor_KiSS-1. 1 hit. [Graphical view] [Entries sharing at least one domain]
ProtoNet	Search...
Other
NextBio	394046.
SOURCE	Search...

Entry information

Entry name

KISS1_MOUSE

Accession

Primary (citable) accession number: Q6Y4S4
Secondary accession number(s): Q149Z8, Q68Y93, Q80XF6

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 2005
Last sequence update:	March 1, 2005
Last modified:	May 1, 2013
This is version 68 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program